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Biomedical subjects

S Reynaud

Publications and source records attributed to S Reynaud.

At least 19 recordsLinked to original sources

3-methylcholanthrene inhibits lymphocyte proliferation and increases intracellular calcium levels in common carp (Cyprinus carpio L).

Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. Many authors have focused on macrophage activities in fish exposed to PAHs. However, fewer studies have reported decrease in specific immunity in such fish. We investigated the intracellular mechanisms by which the 3-methylcholanthrene (3-MC) decreased lymphocyte proliferation in carp. T- and B-lymphocyte proliferation induced by Concanavalin A (Con A) and lipopolysaccharide (LPS) were inhibited by 3-MC (0.5-50 microM). 3-MC also produced a rapid and a sustained increase in intracellular calcium concentration ([Ca(2+)](i)) (2 h minimum). However, the cytochrome p450 1A and Ah receptor inhibitor, alpha-naphtoflavone (a-NF), also inhibited lymphocyte proliferation and did not reverse the effects of 3-MC. Moreover, since a-NF and 3-MC increased [Ca(2+)](i) and inhibited lymphocyte proliferation it was possible that calcium release played a role in 3-MC-inhibited lymphocyte proliferation. The rise in [Ca(2+)](i) induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. Treating cells with 3-MC decreased calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp leucocytes.

Animals↗

The effects of 3-methylcholanthrene on macrophage respiratory burst and biotransformation activities in the common carp (Cyprinus carpio L.).

The sensitivity of phagocytic cell function as a bioindicator of pollution stress by polycyclic aromatic hydrocarbons was evaluated in the common carp (Cyprinus carpio L). The time course response of the head-kidney macrophage respiratory burst was measured 1, 2, 3, 5 and 7 days after intraperitoneal injection of a prototypical Cyp 1A inducer (3-methylcholanthrene). This immune activity was compared to the rate of induction of total cytochrome P450, ethoxyresorufin O-deethylase activity (EROD) and glutathione S-transferase activity (GST) in the liver and head-kidney. 3-methylcholanthrene (40 mg kg(-1)) caused a rapid increase in the macrophage respiratory burst. This response was maximal at day 3 post exposure and coincided with maximum induction of cytochrome P450 and EROD activity in liver and head-kidney. Moreover, alpha-naphtoflavone, which functions as both an Ah receptor antagonist and an inhibitor of cytochrome P450 1A activity, reversed the 3-methylcholanthrene induction of immune and enzymatic parameters measured, suggesting metabolic processes. Taken together these results suggest that the induction of macrophage oxidative function may be an equally sensitive marker of exposure to polycyclic aromatic hydrocarbon as the induction of biotransformation activities and confirm that responses mediated by the Ah receptor are similar, if not identical, to those of mammals.

Animals↗

Lindane increases macrophage-activating factor production and intracellular calcium in rainbow trout (Oncorhynchus mykiss) leukocytes.

The authors studied the in vitro effects of lindane on macrophage-activating factor (MAF) production by peripheral blood leukocytes (PBLs) in rainbow trout. MAF production by PBLs induced normally by mitogens concanavalin A (ConA) and phorbol myristate acetate (PMA) was not modified by a pretreatment with lindane (from 2.5 to 50 microM). Only a concentration of 100 microM lindane decreased MAF production, associated with cellular death. Moreover, MAF activities were detected in supernatants of PBL cultures treated with lindane from 2.5 to 10 microM in absence of ConA/PMA stimulation. Factors present in these supernatants remain to be identified. Lindane, at concentrations which did not induce MAF production (50 and 100 microM) led to an increase in PBL calcium levels by acting on the endoplasmic reticulum calcium stores. Although the intracytosolic calcium concentration ([Ca(2+)](i)) increase seems to be associated with cell death, lindane-induced MAF production may be linked with other intracellular mechanisms.

Animals↗

Lindane-induced macrophage activating factor (MAF) production by peripheral blood leukocytes (PBLs) of rainbow trout (Oncorhynchus mykiss): involvement of intracellular cAMP mobilization.

We studied the in vitro effects of the insecticide lindane (2.5-50 microM) on macrophage activating factor (MAF) production by the peripheral blood leukocytes (PBLs) in rainbow trout. The MAF production induced by the mitogens concanavalin A (ConA) and phorbol-12-myristate-13-acetate (PMA) was not modified by lindane pre-treatment. But lindane alone (2.5-25 microM) stimulated the secretion of MAF by PBLs. Intracellular calcium levels ([Ca2+]i) was measured over 6 min by spectrofluorimetry using Indo-1/AM as fluorescent probe. Lindane (25-100 microM) significantly increased the [Ca2+]i in PBLs, but had no effect on calcium at the dose that caused MAF secretion. Moreover, the effect of lindane on MAF production was potentiated by the inhibitor of phosphodiesterase, isobutylmethylxanthin (IBMX). Lindane also directly increased adenosine monophosphate cyclic (cAMP) in PBLs over the same concentration range that it stimulated MAF production by PBLs. Taken together, these results suggest that lindane increase MAF production by acting on intracellular cAMP concentrations. Moreover, the capacity of this insecticide to act on the [Ca2+]i or on the intracellular concentrations of cAMP according to the dose used could possibly explain its contradictory effects earlier observed on immunity.

Animals↗

3-Methylcholanthrene increases phorbol 12-myristate 13-acetate-induced respiratory burst activity and intracellular calcium levels in common carp (Cyprinus carpio L) macrophages.

Phagocytic cells play a key role in the fish immune system. They secrete reactive oxygen species (ROS) involved in their bactericidal activity. These cells are highly sensitive to pollution by polycyclic aromatic hydrocarbons and other organic pollutants. We have investigated the intracellular mechanisms by which 3-methylcholanthrene (3-MC) increased bactericidal activity of carp phagocytes. Macrophages isolated from head kidney (pronephros) and incubated 1 h with 3-MC enhanced their production of ROS when they were stimulated 1.25 h with phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC). 3-MC also produced a rapid and a sustained increase in [Ca(2+)](i) (2 h minimum). However, the cytochrome P450 1A and Ah receptor inhibitor, alpha-naphtoflavone (alpha-NF), inhibited the potentiation of PMA-induced ROS production, suggesting 3-MC metabolic activation. Moreover, alpha-NF increased [Ca(2+)](i) without macrophage ROS production, suggesting that some mechanism other than calcium release is playing a role in the stimulation of the macrophages by 3-MC. The rise in [Ca(2+)](i) induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. And treating the cells with 3-MC decreased the calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp phagocytes.

Animals↗

Ambulatory 24-hour blood pressure monitoring: correlation between blood pressure variability and left ventricular hypertrophy in untreated hypertensive patients.

BACKGROUND: Left ventricular hypertrophy (LVH) appears to be poorly correlated with clinical measurements of blood pressure: a better correlation may be observed with data from 24 h ambulatory blood pressure monitoring (ABPM). The aim of this study was to compare the results of non-invasive ABPM in a population of patients with essential hypertension who had never been treated, subdividing them based on the presence or absence of LVH in the transthoracic echocardiogram (LVMI, left ventricular mass index > 135 g/m2 in males and > 110 g/m2 in females). METHODS: Eighty hypertensive patients with mild or moderate hypertension underwent routine blood tests, a 24 h ABPM and a transthoracic echocardiogram. Based on the ABPMs, we analyzed average 24 h systolic and diastolic blood pressure (BP), average daytime (6 a.m.-10 p.m.) and nighttime (10 p.m.-6 a.m.) systolic and diastolic BP, average morning (6-12 a.m.) BP and the number of dipper or non-dipper patients. The echocardiographic study included the calculation of left ventricular mass using Devereux's formula according to the Penn convention, analysis of the patterns of left ventricular geometry and a study of left ventricular diastolic function. RESULTS: Thirty-five (43.7%) patients had LVH at the echocardiographic study. In 52 subjects, the clinical history showed at least one BP measurement > 140/90 mmHg in the year prior to our observation. The average age was 48 +/- 11, without any significant correlation to LVMI (r = 0.13). The magnitude of the S-wave in V1 and the R-wave in V5 and the magnitude of the tallest R-wave and S-wave in the electrocardiogram analysis had a significant correlation with LVMI (r = 0.23 and r = 0.26, respectively). The echocardiogram revealed a normal left ventricular geometry in 43.8% of hypertensive patients, concentric remodeling in 13.8%, concentric hypertrophy in 16.2% and eccentric hypertrophy in 26.2%. The isovolumic relaxation time (IVRT) and A-wave were significantly correlated with LVMI (r = 0.49 and r = 0.33, respectively). LVMI had a significant correlation with systolic BP at ABPM (24 h systolic BP r = 0.34; daytime systolic BP r = 0.35; nighttime systolic BP r = 0.28; 6-12 systolic BP r = 0.29) but not with diastolic BP. Dipper patients represented 76.3% of the population, without any difference in LVMI between dippers and non-dippers (p = 0.09). Dipper patients had a higher prevalence of normal left ventricles as compared with non-dippers (p < 0.0001). White-coat hypertension was observed in 7.5% of hypertensive patients. CONCLUSIONS: The prevalence of LVH in our population was high (43.7%) and some parameters related to diastolic left ventricular function (IVRT, A-wave) were correlated with LVMI. Systolic ambulatory BP was significantly correlated with LVMI, while diastolic BP was not.

Adult↗

Id gene activity during Xenopus embryogenesis.

The activity of bHLH transcription factors that are involved in cell determination and differentiation is inhibited by Ids, HLH proteins lacking the basic amino acid sequence element. In order to determine the role of Id during development, we have isolated and characterized the Id genes expressed in Xenopus embryos. Three cDNAs were characterized: XIdIa and XIdIb, which are transcribed from one gene but differentially spliced in the 3' untranslated part, and XIdII which is transcribed from a second copy of the gene. One of the two forms of the differentially spliced mRNAs exhibits, 30 nucleotides upstream from the AATAAA site, a sequence box homologous to the cytoplasmic polyadenylation element (CPE) which is present also in Id2 and Id3 mRNAs from higher vertebrates. This raises the question of whether this CPE-like element may link Id mRNA polyadenylation and translation to the cell cycle metabolism. The Xenopus Id gene is transcribed at low level in oocytes and at high level in embryos, after midblastula transition, in a large number of tissues, including the notochord, neural tube, eye, ear, neural crest cells, presomitic mesoderm, myotomes, tailbud and dorsal fin. In myotomes, expression is high in the areas of proliferating myoblasts and decreases as terminal differentiation proceeds, consistent with a function in cell determination and differentiation and possibly also in cell cycle regulation.

Amino Acid Sequence↗